Lpa receptor antagonists and uses thereof

Patent metadata

Field	Value
Publication number	US-2023212150-A1
Application number	US-202218062363-A
Country	US
Kind code	A1
Filing date	Dec 6, 2022
Priority date	Dec 8, 2021
Publication date	Jul 6, 2023
Grant date	—

Abstract

The present disclosure relates generally to compounds that bind to Lysophosphatidic Acid Receptor 1 (LPAR1) and act as antagonists of LPAR1. The disclosure further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of LPAR1, including fibrosis and liver diseases such as non-alcoholic steatohepatitis (NASH), interstitial lung disease (ILD), or chronic kidney disease (CKD).

First claim

1 . A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

2 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

3 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

4 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

5 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

6 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

7 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

8 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

9 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

10 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

11 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

12 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

13 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

14 . The compound or pharmaceutically acceptable salt thereof of claim 1 , wherein the compound is

15 . A pharmaceutical composition comprising a therapeutically effective amount of a compound, or pharmaceutically acceptable salt thereof of claim 1 , and a pharmaceutically acceptable excipient.

16 . (canceled)

17 . A method of treating, stabilizing, or lessening the severity or progression of an LPAR1 mediated disease or condition comprising administering to a patient in need thereof a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof of claim 1 , or a pharmaceutical composition of claim 15 , wherein the LPAR1 mediated disease or condition comprises fibrosis or is a liver disease.

18 .- 23 . (canceled)

24 . The method of claim 17 , wherein fibrosis is pulmonary fibrosis, renal fibrosis, hepatic fibrosis, ocular fibrosis, cardiac fibrosis, or systemic sclerosis.

25 . The method of claim 24 , wherein pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF) or Progressive Fibrotic interstitial lung disease (PF-ILD).

26 .- 29 . (canceled)

30 . The method of claim 17 , wherein the liver disease comprises liver fibrosis.

31 .- 32 . (canceled)

33 . The method of claim 17 , wherein the liver disease comprises non-alcoholic steatoheptitis (NASH).

34 .- 57 . (canceled)

Assignees

• Gilead Sciences Inc

Inventors

• Bestvater Brian P
• Kaplan Joshua A
• Phillips Barton W
• Yang Kin S
• Zagorska Anna

Classifications

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• A61P43/00 Primary

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P13/12

  of the kidneys · CPC title